Preparation of 2-mercapto thiazoles



- esidue qf he oc an Patented July 15, 1952 2,603,646 rnisreitarlou Z-MERGAPTQ THIAZQLES 1 Roger A. Mathes, Akron,

B. F. Goodrich-Company, ccrnorati uciliewi I ApplicationOctober 18, 1951, SerialNo.251,985 v N0 Draw ng- Ohio,- assignor to The;-

New orka a, (ilaims, (01. cor ect) This invention relates. to a novel reaction of alpha thiocyano: carbonyl compounds.- and. more specifically pertains to the reaction otalphathiocyano cz'aLrbonyl compounds with water-soluble' saltsofdithiocarbamic acicl whereby 'a -2 mercapto thiazole isformed.

'1 have discovered that an alphaethiocyano carbonyl compound, that is, an aldehyde or ketone' having a thiocyano grqupattached to the carbon which is in turn attached to the carbonyl group of the aldehyde or-ketone will-reactwitha watersoluble saltog qithio'carbamic-acid the r se ce of a dilute aqueous solution of" amineral; acid;

water is s plitoutjand; there is produced a 2-mer capto thiazole; Ibis reaction isbelieved; to take placeas-indicated in the followingreaction equation where-HCl is employedto illustrate the-mineral' acid andamm'onium; dithiocarbaniate is employed toillustrate the water-soluble dithiocarbamicacid;= salty;

th f ast where, R nd R2 compr se; the onflea ti a ca b n-32L. G neral y B1 a d R2 r yd o e Q v ydrqcamon dica s namine 1.; toiocarb u tomsi ca sejof the; nat r Qi he di h q j bamate it i pref red that the. reaction be carried out ata tempera ture o r m; Q? .0 3 0! or. at temperat e in qui e r adily- T e notelt 'eaeti nhis: nv nt q prqndes. for p ep r ngv =me tq thiazo es.

eacessioi di hic arbama s.decompos a. 19 W. does. n t nvo ve he use. qi, .chlqnnated.

moi. the methodsroi h print art-1 "iihi'sisi i u arl advantage us o nintmans Qn l method w i h tc i r ar d sc tq s s i 1 thenrsna i o zrnie z pt hiar.

zolesis the reactiorroi an aluharhalqkeiqnewith ammonium dithiocarbamate. The monochloro kton are, i ral; la ma s a d causese i p ci lsas sstmaterialsh pha-chic:

ram r n l c ia un s o the n qn' o not possess any of; these u 'idesirable pr'operties.

Furthermore; the preparation of alpha-chlg rfo ketones involves the useofelementalchlorine, the supply of'which in times of national emergency and/or periods of rapid-expansion in the chemical industry; becomes increasingly short and critical because ofthe" numerous uses; of chlorine for which there is no substitute; The process of this invention will therefore aid -the industry-- appreciably bymaking available a prep-a ar'ation-of well: known and widely-used-jflvula canization accelerators; 2-m'ercapto. :thiazole's; which does not involve the use of chlorinated re'-.-t act-antsv with their undesirable-v physical properties. Y Y

In the processor this invention there can-be. mployed. a y alpharth o y ar onyl ompound- Such a compo nd ,,will of; coursev contain thestructure 1 Y and will have only the one oxygen attached to the arbonyl r n; at m, that iS,,it. will g al ha thiocyano ketone or aldehyde. Ordinarily as, w en t p0S$3SBSthe structur here n R1. andR-ze-hy r enor meantime: groups; however, R1 and R2 may also be radicals 3 containing elements other than carbon and hydrogen present in non-reactive structure, as, for

' example, oxygen in ether linkages, sulfur in thiopounds which are suitable reactants for the proc- V As examples of alpha-thiocyano carbonyl com ess of this invention, there'may be mentioned such alpha-thiocyano-aldehydes as thiocyano j acetaldehyde, alpha-thiocyano-n-propion-aldehyde, alpha-thiocyano-n-butyraldehyde, 1 alphathiocyano n valeraldehyde, alpha isopropyl alpha thiocyano acetaldehyde, alpha benzylalpha thiocyano acetaldehyde, alpha-phenyljalpha-thiocyanoacetaldehyde, alpha-naphthyl alpha-thiocyanoacetaldehyde, alphacyclohexylalpha thiocyano acetaldehyde,' alpha-thiocyanoe' alpha ethoxy acetaldehyde, alpha-thiocyano beta-chlorobutyraldehyde, and alpha-thiocyano beta:ethoxy-butyraldehyde; and such alphathiocyano ketones' as for example 3-thiocyano-pro'; panone-2 3-lthiocyano-butanone-2 V 3-'-thiocyanojpentanone-2; 3-thiocyano-hexanone-2; 3-th iocyano-heptanone-2; 3-phenyl-3-thiocyano-pro-. panone-2; 1 3cyclohexy1-3:thiocyano-propanone 2; 4-phenyl-3-thiocyano-butanone-2; S-phenyl 3-thiocyano-pentanone-2; 6-phenyl-3-thiocyano hexanone -.2; 3-naphthyl 3 e thibcyano-propanone-2'; 5-p-tolyl-3-thiocyano-pentanone-2; 3- thio cyano 4 pentanone-Z; 2-thiocyano-pentanone-3; 2-thioeyano-heXanone-3; l-thiocyanohexanone-2; alpha-thiocyano -propionophenone 1-phenyl-3-thiocyano-butanone 2; 'l-phenyl-ithiocyano pentanone-3 alpha thiocyano-proe piononaphthone; ithiocyano-hexanone-B; 3- thiocyano-heptanone-i; 2-thiocyano octanone-3 alpha-thiocyano pentanophenone;. 1 phenyl-3- thiocyano-pentanone-2; 1 phen'yl-4-thiocyanohexanone 3; alpha thiocyano pentanonaphthone; 5-thiocyano-1-heptenone-4; 1-cyclohexyl-' l-thioeyano-propanone; 1 cyclohexyl 2 thiocyano-p'ropanoney 1-- cyclohexyl 2 thiocyanobutanone; '1 methoxy-B-thiocyano-butanone-2 1- (methyl-'thio) 3-thiocyano-butanone-2; 2'-thi ocyano-1-isopropoxy-butanone-3; 2-thiocyano-1- (isopropyl-thio) butanone 3; 2 thiocyano-lethoxy-butanone-JS; Z-thiocyano-l- (ethyl-thio) butanone-3; 2-thiocyano-1-o-nitro-phenyl-buta none-3; 2 thiocyano-1,5-di-phenyl-6-nitrohexanone-3; 3 thiocyano 1-butoxy-2-methylhexanone-4; 4-thiocyano-1-ethoxy 5 methylhex'a' none-3; 2 thiocyano-cyclopentanone Z-thiocyano 'cyclo hexanone; 2,5 di(thiocyano) 1,4-

1 cyclohexanedione; 2,3 -.di(thiocyano) -1,4cycl0- I hexanedione; 2,3 di(thiocyano)-1,4-pentanedi one; 2,5-di(thiocyano)-1,6-decanedione; and 2- (alpha-thiocyano-acetonyl) -cyclohexanone.

Although any alpha-thiocyano carbonyl compound containing the structure hereinbefore set forth can be employed as a reactant according to the process of this invention, the alpha-thiocyano ketones, where R1 in the general formula hereinbefore appearing is a hydrocarbon group, are pre- 'duce' a Z-mercapto thiazole.

4 ferred as reactants because at more readily available.

Any of the mineral acids, such as hydrochloric, sulfuric, phosphoric and other mineral acids can be employed in the process of this invention; hydrochloric .acid is the preferred mineral acid for this process. The quantity of acid to be employed in the process of this invention can be varied from 1.0 mole to 2.0 moles per mole of the alpha-thiocyano carbonyl compound present.

Any water-soluble saltof dithiocarbarnic acid c'anbe -,employd ,;jas a reacta'n t "e 'process of this invention; ex'ar'nple, fsodium dithiocarbamate, potassium dithiocarbamate and ammonium dithiocarbamate among vothers can be reacted with the alpha-thiocyano carbonyl to pro- However, all the water-soluble salts of dithiocarbamic acid are, in

present they are general, made from ammonium dithiocarbamate,

-.Th 'e quantity of reactants to be employed is not critical and can be varied according to the *siz'e'of' th'e reaction equipment tobe employed.

Regardless of the quantity. of 2-mercapto thiazole to be prepared, it will, in-.general,- be found toebe most advantageous to, employ from substantially, equimolecular portions'of thegreactant to a 20%:

excess of thewater-soluble dithiocarbamatarthat is from-1.0 mole to'1;2 moles'of the dithiocarrbamate per mole of .thiocyano' carbonyl. a The following specific example'will illustrate the details of .the process ofthisi To a reactor there was added-.133 .partsaby. weight of an aqueous solutioncontainingfiparts by Weight (0.22 mole) of HCl and2'5.8 ;parts. byweight (0.2 mole) of eB -thiocyanO-butanone-Z. This mixture-Was stirred and cooled toa tempera-. ture between 5 and 10. C. Therewas slowly added to this cooled mixture over a period'pf one hour 29 parts-by weight nvention. -1

carbamate (0.26 mole). The resultingreaction mixture was stirred and maintained at a temperature of from 5 to 10 C. for this period of addition of the dithiocarbamate. A gummy precipi tate formed during the addition of the dumbcarbamate. The recation mixture 'was stirred for an additional hour, removed from the reactor and filtered. The precipitate recovered was oily and contained some unreacted,3-thiocyano-butanone-2, which was removed from the precipitate by washing it with hexane to extract the unreacted thiocyano-butanone. The resulting product was in the form of white crystals which melted at 157 to 160 C- After the crystals Were washed with benzene theirmelting point was 160 to 162 0. These crystals were mixed with, authentic The product formed by this preparationfwa's, therefore, 2-'mercapto}4,5 dimethylthiaaole.

The following 'examples in tabular ,form are presented to' illustrate the variety of 2I-mercapto thiazoles which can be prepared according to 'the process of this invention, In all these examples ammonium dithiocarbamate is, the water-soluble dithiocarbamic acidsalt employed as a reactant with the alpha-thiocyano carbonyl compound although as it will be readily understood any water. soluble salt of. dithioc arbainic acid an .be le'm. ployedj'as'aeactant- Thusonly the thiocyano carbonyl is specifically named. I i

of-an. aqueous solution. containing 20% by weight of ammonium-.dithioe;

Products of reaction of ammonium dithiocarbamate with an aZpha-thiocyano carbonyl compound gg Thiocyano Carbonyl Product 1-thiocyanobutanone-2 2-Inercapto-4-ethylthiazole. Thiocyano acetaldehyde Z-mercaptothlazole. Alpha-thiocyano propionaldehyde z-mercapto--Inethylthiazole.

Z-isopropyl-Z-thiocyano acetaldehyde 2-pheny1-2-thiocyano acetaldehyde. B-thiocyano hexanone-2 4-phenyl-3-thiocyano-butano11e-2. 2-thiocyano-heptanone-3 Alpha-thiocyano propionophenone O Hl-CH-CH:

Alpha-thiocyano propiononaphthone 3-thiocyano-octanone-4 1-phenyl-4-thiocyano hexanone-li.

5-thiocyano-l-heptenone-4 3-thiocyano-4-hexenone-2 2-mercapto-5-isopropylthiazole.

. 2-mercapto-5-phenylthiazole.

Z-mermpto-5-propyl-4-methyl-thiazolel Z-mercapto-5-benzy1-4-methyl-thiazole. 2-mereapto4-methyl-5-n-buty1thiazole.

2-mercapt0-4-naphthyl-5-methyl-thiazole.

2-mercapto-*i-butyl-dethyl-thiazole. Z-mercapto-4-phenethyl-5-ethyl-thiazole. 2-mercapto-tallyl-5-ethyl-thiazo1e. 2-111ereapto--methyl-b-allyl-thiazole.

Any of the thiocyano carbonyl compounds of the class hereinbefore defined can be employed as a reactant in place of those employed in the above examples to produce the corresponding 2- mercapto thiazole. I

Although I have illustrated my invention with the preparation of certain specific 2-mercapto thiazoles, I do not thereby desire or intend to limit myself solely thereto, for as hitherto stated reactants which are the chemical equivalents of those employed may be substituted for the specific reactants and the precise proportions of the reactants can be varied, if desired, without departing from the spirit and scope of the invention as defined in the'appended claims.

I claim: 7 p I p 1. The method which comprises reacting an alpha-thiocyano carbonyl compound with a we.- ter-soluble salt of dithiocarbamic acid in the presence of a dilute aqueous solution of a mineral acid thereby to form a Z-mercapto thiazole.

2. The method which comprises reacting an alpha-thiocyano carbonyl compound having the structure wherein R1 and R2 are members selected from the group consisting of hydrogen and hydrocarbon groups containing from 1 to 10 carbon atoms, with ammonium dithiocarbamate in the presence 0! a dilute aqueous solution of HCl thereby to form a Z-mercapto thiazole, and recovering said thiazole.

3. The method of claim 2 where the alphathiocyano carbonyl compound is an alpha-thiacyano ketone and R1 and R2 are hydrocarbon groups containing 1 to 10 carbon atoms.

4. The method which comprises reacting 3- thiocyanobutanone-2 with ammonium dithiocarbamate in the presence of a dilute aqueous solution of H01 thereby to formZ-mercapto-j-dimethylthiazole, and recovering this thiazole.

ROGER A. MATHES.

No references cited. 

1. THE METHOD WHICH COMPRISES REACTING AN ALPHA-THIOCYANO CARBONYL COMOPOUND WITH A WATER-SOLUBLE SALT OF DITHIOCARBAMIC ACID IN THE PRESENCE OF A DILUTE AQUEOUS SOLUTION OF A MINERAL ACID THERERBY TO FORM A 2-MERCAPTO THIAZOLE. 